University of Cambridge > Talks.cam > Boris Lenhard seminar >  Long- and short-range gene regulation: from genome-wide patterns of sequence conservation to the dynamics of regulatory complexes

Long- and short-range gene regulation: from genome-wide patterns of sequence conservation to the dynamics of regulatory complexes

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The accumulation of data on highly-conserved long-range enhancers, as well as the genome wide transcription factor binding and epigenetic modification data from ChIP experiments, has begun to dismantle the textbook picture of transcriptional regulation by transcription factors binding to either proximal promoter regions or distal upstream enhancers. Highly conserved enhancers of developmental genes can drive the expression of their target genes from megabase distances, often with one or more unaffected genes in between. As the ChIP-seq data confirms, transcription factors are often found to bind inside long introns, especially the first intron of metazoan genes that is also the longest on average. At the same time, many expression patterns of tissue-specific genes can still be recapitulated using only its short upstream sequence pit in front of a reporter gene. We have investigated the distribution of binding locations of regulatory complexes driving expression of different functional categories of genes and the effect of their position on the activity of their target genes and other genes in their neighborhood. The results indicate that the responsiveness of genes to long-range regulation strongly depends on the type of their core promoter and represents a defining property of several functionally distinct classes of genes. This helps explain the evolutionary patterns of gene and genome duplications, and has implications for the planning and interpretation of studies of gene regulation and genome-wide disease association.

This talk is part of the Boris Lenhard seminar series.

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